1. Field of the Invention
The present invention relates to medical devices and, more particularly, to topographic surfaces for medical devices such as catheters that prevent bacterial fouling.
2. Description of the Related Art
Bacteria have remarkable capabilities to attach to both biotic and abiotic surfaces and form multicellular structures with cells embedded in polymeric substances. Such complex sessile communities are known as biofilms and are found ubiquitously in aqueous environments. Biofilms are up to 1,000 times more resistant to antimicrobial agents than planktonic (free-swimming) bacteria of the same genotype. These multicellular structures are involved in 80% of bacterial infections in humans and play an important role in the spread of antimicrobial resistance due to biofilm-associated horizontal gene transfer. As a result, biofilms are a major cause of chronic infections and responsible for 99,000 deaths and 28-45 billion dollars of healthcare cost in the U.S. annually. Common medical devices such as catheters, prosthetic heart valves, joint prostheses, cardiac pacemakers, and many others are all at risk of biofilm infections. Due to the significance of biofilms, effective strategies for biofilm prevention and removal are urgently needed.
Catheters are one of the most widely used medical devices, and are frequently used for urine retention on an intermittent or indwelling basis. Urinary tract infections account for around 40% of noscomial infections, the majority of which are catheter-associated urinary tract infections (CAUTIs). The recent US multistate point-prevalence survey of healthcare-associated infections revealed that urinary tract infections (UTIs) are the fourth most common infection, and 67.7% of UTI patients had a urinary catheter. Despite the prevalence, the National and State Healthcare-associated Infections Progress Report published by CDC in 2014 also revealed an alarming 3% increase in CAUTI cases between 2009 and 2012.
Controlling nosocomial infections is challenging due to the compromised immunity among hospitalized patients and increased prevalence of drug resistant bacteria. Thus, novel devices and materials for effective control and prevention of nosocomial infections are acutely needed for life saving and recovery of infected individuals. This is also important for preventing the spread of multidrug resistant bacteria to the general public.
CAUTI occurs when an urinary catheter is not inserted or cleaned properly, left in the patient for too long, or not monitored correctly, leading to exposure to microbes which travel through the catheter by motility and cause infection of the patient. The most common microbial species involved in CAUTIs are Escherichia coli, Candida spp, Enterococcus spp, Pseudomonas aeruginosa, Klebsiella pneumonia, Enterobacter spp, Proteus mirabilis, and Staphylococcus spp. Bacteria establish infections by adhering to the catheter with flagella, pili, and adhesions. Attachment of bacteria leads to the subsequent formation of biofilms, which are surface-attached multicellular structures formed by microbes comprised of an extracellular matrix secreted by the attached cells. For example, the urease-forming bacterium P. mirabilis can form an extensive biofilm generating ammonia from urea and elevating the pH of urine. Due to rise in pH, crystals of calcium and magnesium phosphates precipitate in the urine and the catheter biofilm. This crystalline biofilm poses even further damage by initiating stone formation and septicaemia. Thus, in addition to the impact on quality of life, CAUTIs also cause a heavy financial burden on the health care system due to increase in treatment time and length of hospital stay.
Biofilms are difficult to treat due to extremely high tolerance of biofilm cells to antimicrobials and disinfectants (up to 1000 times higher compared to their planktonic counterparts). The close contact between biofilm cells also provides an ideal condition for bacterial horizontal gene transfer through conjugation, a process that mobile DNA elements carrying drug resistance genes are transferred between different bacterial species, leading to the emergence of multidrug resistant bacteria including “superbugs”. Thus, it is extremely important to develop new control methods to prevent biofilm formation on indwelling medical devices.
Although biofilm formation has been extensively studied, biofilm control is still challenging. It is well known that biofilm formation is a dynamic process including attachment, microcolony formation, maturation, and dispersion (FIG. 1).
Recent research has shown that biofilm formation can be influenced by many factors of the substratum surface such as surface chemistry, topography, hydrophobicity, and charge. As an important surface property, surface roughness plays important roles in microbial adhesion and biofilm formation. However, the exact effects of surface roughness on bacterial adhesion and biofilm formation vary with the size and shape of bacterial cells and other environmental factors. Increasing data have shown that the conventional definition of roughness based on the average amplitude of peaks and valleys is not sufficient to describe the 3D feature of a surface and the distribution of peaks and valleys is also important to microbial biofilm formation. Recent advancements in material and surface engineering have brought exciting opportunities to create surfaces with not only controlled overall roughness, but also well-defined topographic patterns to control biofilm formation. In addition to the well-known example of Sharklet surfaces (with microscale topographic patterns inspired by the skin of shark), a number of μm- and nm-scale topographic patterns with varying shape and size have been shown to inhibit biofilm formation compared to flat surfaces of the same material, such as protruding and receding squares, circles, and parallel channels on polydimethylsiloxane (PDMS), cone-shaped patterns of silicone, ridges on PDMS, strain-induced wrinkles on PDMS, and circular poles on polystyrene. Some well-defined nanostructures can also lead to superhydrophobicity (Cassie state) and reduce biofouling. Despite the promise, how bacteria respond to surface topography is still poorly understood. As a result, the currently available topographic surfaces are largely based on empirical tests rather than rational design, lack of long-term activities, and are difficult to apply to catheter manufacturing. Thus, there is a need in the art for surface topographies that are designed to resist bacterial adhesions and biofilm formation in devices such as urinary catheters.